Genomic profiling of budding yeast resistance to food carcinogens underscore the importance of DNA damage tolerance pathways in avoiding mutations

We profiled the yeast genome for resistance to cytochrome P450-activated carcinogens. We introduced the human CYP1A2 and NAT2 genes into approximately 90% of the diploid non-essential deletion collection. We identified resistance genes by screening the entire pooled collection after exposure to aflatoxin B1 and heterocyclic aromatic amines. Resistance genes were confirmed by growth curves and placed in gene ontology groups. Interestingly, we found DNA damage tolerance genes to be common among multiple screens, among which were RAD18. We identified the SHU complex in a screen to identify aflatoxin resistance genes and observed that csm2 mutants exhibited higher levels of aflatoxin B1-associated mutagenesis. We suggest that the SHU complex functions in tolerating aflatoxin-associated bulky adducts, similarly as was observed for alkylated bases. Additional screens are in progress to identify resitance genes for heterocyclic aromatic amines associated with colon cancer incidence.